Forum for Science, Industry and Business

A CNIO study tracks the evolutionary history of a cancer-related gene

06.06.2013

The study reveals how a genetic duplication that occurred millions of years ago encouraged the evolution of the ASF1b gene, involved in cancer development

How and when evolution generates diversity or gives form to proteins, living beings' functional building blocks, are essential questions that still surround the theory of evolution. In humans, the majority of genes have emerged via genetic duplication, a strategy in which a gene generates two identical copies that can evolve to generate different proteins.

A study published today by scientists from the Spanish National Cancer Research Centre (CNIO) describes how a genetic duplication that took place in the vertebrate ancestor some 500 million years ago encouraged the evolution of the ASF1b gene; a gene essential for proper cell division and related to some types of cancer such as breast cancer. The results of the study are published in Molecular Biology and Evolution, one of the most prestigious journals in the field of molecular biology and evolution.

The conclusions of the study are the result of collaboration between the team led by Alfonso Valencia, Vice-Director of Basic Research and Director of CNIO's Structural Biology & Biocomputing Programme, and the team led by Genevieve Almouzni, a member of CNIO's Scientific Advisory Committee, at the Institut Curie in Paris, France.

Valencia says that: "When proteins have such a close similarity as the one that exists between the two human copies of the ASF1 gene—ASF1a and ASF1b—it is commonly assumed that they have similar functions in cells; in this case related to fundamental processes such as DNA remodelling and repair, cell division, cell proliferation and genetic transcription or activation".

THE GENOMIC ENVIRONMENT, KEY TO SUCCESS IN SEPARATING FUNCTIONS

Almouzni's team discovered several years ago that, despite the similarity in structure, the two copies of ASF1 were not redundant, but rather had divided up their ancestral functions. How and why, though, did this specialisation happen, and what biological advantages were conferred on the cells?

The authors of the study have used sophisticated ancestral state reconstruction methods in order to track the evolutionary history of ASF1 from its duplication. To this end, they have studied the genome of up to 40 species, some of them as diverse as sea urchins, lampreys, fish, frogs or a wide spectrum of mammals and birds.

Federico Abascal, first author of the study, explains that: "Our results suggest that ASF1b is the original copy that was duplicated millions of years ago. Following the duplication, the other copy moved twice within the genome, settling in very different surroundings to the original". Daniel Rico, one of the study's authors, adds that: "It is precisely this localisation of the two genetic duplicates in such different genomic environments that possibly opened up the door for ASF1b and ASF1a to follow different paths".

According to the researchers, the new genomic context and positive selection are responsible for the subtle differences between the two proteins, which are those that allow them to develop different functions.

"This function separation process put an end to the adaptive conflict in the ancestral gene, which should have simultaneously carried out very different competitive functions that were indispensable for the cells", says Valencia.

The researchers point out that studying the molecular history of genes is fundamental to understanding how they adapt to the functions they develop. In the case of proteins as important as ASF1, this knowledge is crucial for establishing the process of its deregulation in cancer.

Die letzten 5 Focus-News des innovations-reports im Überblick:

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...